Antihypertensive Prescribing Patterns for Adolescents With Primary Hypertension

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1 ARTICLE Antihypertensive Prescribing Patterns for Adolescents With Primary Hypertension AUTHORS: Esther Y. Yoon, MD, MPH, a Lisa Cohn, MS, a Albert Rocchini, MD, b David Kershaw, MD, c Gary Freed, MD, MPH, a Frank Ascione, PhD, PharmD, d and Sarah Clark, MPH a Divisions of a General Pediatrics, Child Health Evaluation and Research (CHEAR) Unit, b Pediatric Cardiology, and c Pediatric Nephrology and d School of Pharmacy, University of Michigan, Ann Arbor, Michigan KEY WORDS hypertension, adolescents, primary care, specialty differences, antihypertensive prescribing ABBREVIATIONS ACE angiotensin converting enzyme inhibitor ARB angiotensin receptor blocker BB b-blocker BP blood pressure CI confidence interval CVD cardiovascular disease DIU diuretic HTN hypertension ICD-9-CM International Classification of Diseases, Ninth Revision, Clinical Modification OR odds ratio PCP primary care physician Spec subspecialist The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. doi: /peds Accepted for publication Sep 9, 2011 Address correspondence to Esther Y. Yoon, MD, MPH, Child Health Evaluation and Research (CHEAR) Unit, University of Michigan, 300 N Ingalls St, Room 6E07, Ann Arbor, MI est@med.umich.edu PEDIATRICS (ISSN Numbers: Print, ; Online, ). Copyright 2012 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. Funded by the National Institutes of Health (NIH). WHAT S KNOWN ON THIS SUBJECT: Primary hypertension is a growing concern in adolescents due to its association with the obesity epidemic. Recent studies have examined underdetection and underdiagnosis of hypertension in adolescents but medical management of primary hypertension in adolescents is not welldescribed. WHAT THIS STUDY ADDS: Our study describes patterns of antihypertensive prescribing for adolescents with primary hypertension including the use of monotherapy versus combination therapy by physicians of different specialties and factors associated with receipt of antihypertensive therapy over a multi-year period. abstract BACKGROUND: Hypertension is an increasingly common problem in adolescents yet current medical management of primary hypertension in adolescents has not been well-described. METHODS: We identified adolescents with primary hypertension by International Classification of Diseases, Ninth Revision codes and looked at prescription patterns chronologically for antihypertensive drug class prescribed and the specialty of prescribing physician. We also examined patient demographics and presence of obesity-related comorbidities. RESULTS: During , there were 4296 adolescents with primary hypertension (HTN); 66% were boys; 73% were aged 11 to 14 years; 53% were black, 41% white, and 4% Hispanic; and 48% had obesity-related comorbidity. Twenty-three percent (977) received antihypertensive prescription. White subjects (odds ratio [OR]: 1.61; confidence interval [CI]: ), older adolescents ($15 years, OR: 2.11; CI: ), and those with comorbidity (OR: 1.57; CI: ) were more likely to receive antihypertensive prescriptions controlling for gender and years of Medicaid eligibility in logistic regression. Angiotensin converting enzyme inhibitors were the most frequently prescribed monotherapy. Nearly two-thirds of adolescents received prescriptions from adult primary care physicians (PCPs) only. More than one-quarter of adolescents who received a prescription received combination therapy, which was most often prescribed by adult PCPs. CONCLUSIONS: Adult PCPs were the leading prescribers of antihypertensives for adolescents with primary HTN. Race differences exist in physicians prescribing of antihypertensives to adolescents with primary HTN. The choice of antihypertensives by physicians of different specialties warrants additional study to understand the underlying rationale for treatment decisions and to determine treatment effectiveness. Pediatrics 2012;129:1 8 PEDIATRICS Volume 129, Number 1, January

2 There is growing concern about elevated blood pressure (BP) and hypertension (HTN) in adolescents because of its association with the obesity epidemic, which is estimated as affecting one-third of American adolescents. 1 3 Moreover, HTN in adults is a known risk factor for cardiovascular disease (CVD), one of the leading causes of morbidity and mortality in American adults. 4 Recent studies have examined issues of underdetection and underdiagnosis of HTN in adolescents. 5,6 However, current medical management of primary HTN in adolescents has not been well described. Pediatric guidelines (2004) recommend initiating antihypertensive drug therapy in adolescents who have persistent HTN despite lifestyle modifications, using monotherapy from any of the 5 common antihypertensive drug classes: angiotensin converting enzyme inhibitors (ACEs), angiotensin receptor blockers (ARBs), b-blockers (BBs), calcium channel blockers, and diuretics (DIUs); importantly, there is no prioritization of drug choice. 7 Guidelines also recommend consideration of combination drugs if the desired BP goal is not achieved on monotherapy. It is unknown which antihypertensive medications are prescribed for treatment of primary HTN in adolescents and whether pharmacotherapy varies by the specialty of prescribing physician and/or patient characteristics such as demographics and presence of comorbidities. The purpose of this study was to describe the use of antihypertensive pharmacotherapy to treat primary HTN in adolescents and the associated physician and patient characteristics. Our assumption was that subspecialty physicians, such as pediatric cardiologists and nephrologists, would most frequently prescribe antihypertensive medications to adolescents with primary HTN and that adolescents with comorbidities, such as obesity and diabetes would more likely receive antihypertensive therapy compared with those without comorbidity. METHODS Study Design We conducted longitudinal analysis of Michigan Medicaid outpatient claims and pharmacy data from 2003 through 2008 for adolescents aged 12 to 18 years. We identified adolescents with primary HTN by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes and examined antihypertensive prescription patterns chronologically for antihypertensive drug class prescribed (if any) and the specialty of the prescribing physician. This study was approved by the Institutional Review Board of University of Michigan Medical School. Study Population The sampling frame was adolescents aged 12 to 18 years on December 31, 2003, who were eligible for Michigan Medicaid for at least 3 of 6 years ($11 months per year) during the period We included both fee-forservice and managed care Medicaid coverage and included those with dual Title V eligibility. We excluded years in which children had other insurance coverage. We considered adolescents to have primary HTN if they had an outpatient clinic visit claim with an ICD-9-CM code for either HTN (401.3) or elevated BP without HTN (796.2). 5 We excluded adolescents who had $1 visits with an ICD-9-CM code for malignant HTN, pregnancy-related HTN, portal HTN, pulmonary HTN, glaucoma, and secondary HTN; we also excluded adolescents who had $1 visits with an ICD-9-CM code for common pediatric causes of secondary HTN such as renal disease, coarctation of aorta, hyperthyroidism, Cushing s syndrome, and pheochromocytoma. A full list of exclusion codes is found in the Appendix. We also excluded adolescents who had any pharmacy claims for clonidine or guanfacine to focus on physician prescribing of 5 common antihypertensive drug classes recommended for treatment of pediatric HTN. Variables of Interest Pharmacy claims for the duration of Medicaid eligibility were acquired; claims included National Drug Codes and prescriber identifiers. Companion data files were used to link prescriber identification numbers with physician specialty data; specialty was categorized as adult primary care physicians (PCPs; family physicians, general practitioners, internists, medicine-pediatrics), pediatric PCPs (general pediatricians), subspecialists (Specs; both adult and pediatric subspecialties including but not limited to cardiology, nephrology, emergency medicine, endocrinology, rheumatology), and unknown. From this analytic file, we created the following variables: Receipt of $1 prescription for an antihypertensive drug during the study period; Class of antihypertensive prescription: each prescription was categorized as 1 of 5 classes recommended for pediatrics; Antihypertensive monotherapy versus combination therapy: (1) monotherapy was defined as having prescription claims for only 1 antihypertensive medication per day. Adolescents who were switched from1antihypertensivesingledrug to another were categorized according to the drug class of the last antihypertensive prescription claim, to allow mutually exclusive groups. (2) Combination therapy was defined as prescription claims for 2 drug classes on the same or 61 day; a repetitive pattern of 2 YOON et al

3 ARTICLE prescription claims for 2 drug classes; or $1 prescription claim for a combination antihypertensive medication (ie, 1 medication formulated with 2 antihypertensive drugs, such as Lotensin HCT). Adolescents who received combination therapy at any time during the study period were classified as having combination therapy, even if they had periods of monotherapy; Mean and median number of antihypertensive prescriptions filled per year of Medicaid eligibility; Drug class of first antihypertensive prescription; Age at first antihypertensive prescription; Time between first monotherapy prescription and first combination therapy prescription; Combination therapy as 1 pill versus multiple drugs; Duration of Medicaid eligibility (3 years vs 4 6 years); and Prescriber specialty across all antihypertensive prescriptions during the study period, categorized as adult PCPs only, general pediatric PCPs only, Spec only, both PCP and Spec, both adult PCP and pediatric PCP, and unknown. Independent Variables Demographic variables included age at start of Medicaid eligibility during categorized as younger (11 14 years) versus older adolescents (15 19 years); race categorized as white, black, Hispanic, and other/unknown; and gender. Given that the sampling frame was age years on December 31, 2003, it was possible for adolescents who were aged 11 years or 19 years at start of their Medicaid eligibility to be included in the study. Adolescents could have had a diagnosis of HTN at any point during the 3+ years of Medicaid eligibility from 2003 to Thus, age at first HTN diagnosis does not necessarily equal age at start of Medicaid eligibility. Presence of obesityrelated comorbidities was defined as having $1 visits with an ICD-9-CM code for obesity, hyperlipidemia, type 2 diabetes mellitus, or metabolic syndrome. Statistical Analysis Descriptive analyses included simple counts and proportions. We used x 2 tests to assess associations between receipt of antihypertensive prescription and demographic characteristics, and choice of antihypertensive drug class prescribed and prescribing physician specialty. We performed multivariate logistic regression to evaluate the associations between demographics and receipt of antihypertensive prescription, among all adolescents with primary HTN. We also performed multivariate logistic regression to evaluate the associations among demographics, prescribing physician specialty, and receipt of combination antihypertensive therapy among the subset of adolescents who received at least 1 antihypertensive prescription. P values #0.05 were considered statistically significant. All analyses were performed using SAS version 9.2. RESULTS On December 31, 2003, there were adolescents aged 12 to 18 years enrolled in Michigan Medicaid program, of which had at least 3 years of enrollment ($11 months of Medicaid eligibility and no other insurance for each study year) during From this, we identified 8549 adolescents with a diagnosis of primary HTN at an outpatient visit then excluded those with secondary causes of HTN and receipt of clonidine or guanfacine prescription, resulting in our final study sample of 4296 adolescents. Study Sample Characteristics For the 4296 adolescents who met eligibility criteria, two-thirds were boys; 73% were aged 11 to 14 years at start of Medicaid eligibility; and 53% were black, 41% white, and 4% Hispanic (Table 1). The majority of our study sample (n = 3806) had a diagnosis of HTN (401.3), and 490 adolescents had elevated BP without HTN (796.2) with no difference in demographics. Our sample demographics (n = 4296) were also similar to the Medicaid population in general with the exception of gender; one-third of our sample were girls, whereas gender was more evenly distributed in the general Medicaid population. Nearly half had an obesity-related comorbidity (48%). One-third of adolescents had 6 years of Medicaid eligibility, with 80% enrolled during the first year (2003) of the study period (Table 1). During the study period, 23% of adolescents in our sample (n = 977) received at least 1 antihypertensive prescription. A quarter of the 3806 with HTN diagnosis (401.3) received antihypertensive TABLE 1 Demographic Characteristics of Adolescents with $3 Years of Medicaid Eligibility and Primary HTN Diagnosis During (N = 4296) Overall, n (%) Gender Male 2828 (66) Female 1468 (34) Race White 1757 (41) Black 2279 (53) Hispanic 164 (4) Other/unknown 96 (2) Obesity-related comorbidity Yes 2063 (48) No 2233 (52) Age at first eligibility, y (73) (27) Duration of Medicaid eligibility, y (21) (22) (23) (34) First y of eligibility (80) (20) Age at first HTN diagnosis, y (16) $ (84) PEDIATRICS Volume 129, Number 1, January

4 prescriptions compared with 5% of the 490 with elevated BP without HTN (796.2). Thus, adolescents with elevated BP without HTN did not significantly affect the overall number of adolescents who received antihypertensive prescriptions in our study. Characteristics associated with adolescents who received antihypertensive prescriptions are presented in Table 2. Older and white adolescents were more likely than younger and black adolescents to receive an antihypertensive prescription. Adolescents with obesity comorbidity also were more likely to receive an antihypertensive prescription. Mean and median antihypertensive prescriptions filled per year of Medicaid eligibility were 2.4 and 1.2, respectively. This did not vary significantly by gender; however, white subjects (mean 2.9, median 1.4) and older adolescents (mean 3.3, median 1.5) had higher mean and median prescriptions per year of eligibility compared with black subjects (mean 1.9, median 0.8) and younger adolescents (mean 1.9, median 0.8; P,.0001). Antihypertensive Prescriptions for Adolescents With Primary HTN (n = 977) Overall, mean and median age at first antihypertensive prescription was similar at 16.9 and 17 years, respectively, and did not vary significantly by gender, race, or presence of obesity-related comorbidity. Among adolescents who received antihypertensive prescription, 86% (n = 839) initially received monotherapy; 72% (n = 701) continued with monotherapy only during the study period, with ACE as the most frequently prescribed drug class (Table 3). Twelve percent of the monotherapy-only group was switched from the initial antihypertensive monotherapy to a different monotherapy drug class during the study period, most often from diuretics and BB to ACE. TABLE 2 Characteristics Associated With Receipt of Antihypertensive Prescription During Adolescents With Primary HTN Who Received x 2 P Value Antihypertensive Prescription, % Overall (n = 4296) 23 Gender.1706 Male (n = 2828) 23 Female (n = 1468) 22 Race,.0001 White (n = 1757) 28 Black (n = 2279) 19 Hispanic (n = 164) 25 Other/unknown (n = 96) 17 Obesity-related comorbidity,.0001 Yes (n = 2063) 27 No (n = 2233) 19 Age at first eligibility, y, (n = 3126) (n = 1170) 33 Duration of Medicaid eligibility, y (n = 880) 26 4(n = 944) 23 5(n = 999) 22 6(n = 1473) 21 First y of eligibility (n = 3441) (n = 855) 23 Age at first HTN diagnosis, y (n = 692) 19 $15 (n = 3604) 24 Combination antihypertensive therapy was prescribed at some point in the study period for 28% (n = 276) of adolescents who received any antihypertensive prescription. Of the 276 adolescents who ever received combination therapy, 50% (n = 138) had combination antihypertensives as the first prescription identified during the study period, 30% (n =84)received combination therapy within the first year of receiving monotherapy, and 20% (n = 54) received combination therapy $1 to 6 years after receiving monotherapy. The 3 most commonly prescribed drug combinations were ACE-DIU, DIU-DIU, and BB-DIU combinations. Among adolescents who ever received combination therapy, 68% (n = 188) were prescribed 1-pill combination drugs (Table 3). Physician Specialty (n = 977) Nearly two-thirds of adolescents with primary HTN with antihypertensive prescription received prescriptions from adult PCPs only (Table 3). Ten percent of adolescents received their antihypertensive prescription only from Specs, and 5% received their antihypertensive prescription only from pediatric PCPs. Adult PCPs (62%) were also leading prescribers of combination antihypertensives, whereas Specs (7%) and pediatric PCPs (3%) prescribed fewer combination antihypertensives (Table 3). Adolescents who received antihypertensive prescriptions from physicians of multiple specialties during the study period were more likely to receive combination therapy versus monotherapy (42% from both PCPs and Specs, n = 57; 34% from both adult PCPs and pediatric PCPs, n = 11) compared with those receiving prescriptions from adult PCPs only (28%, n = 172), Specs only (20%, n = 19), and pediatric PCPs only (16%, n =7;P,.0001; Table 3). Among the subset of adolescents receiving combination therapy, those 4 YOON et al

5 ARTICLE TABLE 3 Medicaid Adolescents With Primary HTN and Antihypertensive Prescription, by Drug Class and Prescribing Physician (n = 977) ACE ARB BB CCB DIU Combo Total (%) One Drug Multiple Drugs Adult PCP only (63) Pediatric PCP only (5) Spec only (10) Both PCP + Spec (14) Both adult PCP + pediatric PCP (3) Unknown (5) Total 258 (26%) 6 (1%) 165 (17%) 77 (8%) 195 (20%) 276 (28%) 977 CCB, calcium channel blockers; Combo, combination antihypertensive drugs. P # who received prescriptions from physicians of multiple specialties during the study period (both adult PCP + pediatric PCP and both PCP + Spec groups) were also more likely to receive combination therapy as multiple drugs than as 1 pill compared with those receiving combination therapy from physicians of single specialty with the exception of unknowns (Table 3). Prescription of combination therapy as 1 pill versus multiple drugs did not vary significantly by race, age, and gender. Multivariate Logistic Regression Analysis Among all adolescents with primary HTN, receipt of antihypertensive prescriptions was significantly associated with age, race, and presence of obesityrelated comorbidity in our multivariate logistic regression model (Table 4). Controlling for patient gender and years of Medicaid eligibility, older adolescents, those with obesity-related comorbidities, and white subjects were more likely to receive antihypertensive prescriptions compared with younger adolescents, those without obesity comorbidity, and black subjects. Among the subset of adolescents who received antihypertensive prescriptions, receipt of combination therapy was significantly associated with age, gender, race, and prescribing physician specialty in our multivariate logistic regression model (Table 5). Controlling for obesity comorbidity and years of Medicaid eligibility, older adolescents, girls, black subjects, and adolescents who received prescriptions from both PCPs and Specs were more likely to receive combination therapy compared with younger adolescents, boys, white subjects, and adolescents who received prescriptions only from Specs. DISCUSSION Our study describes for the first time the proportion of adolescents with primary HTN who receive antihypertensive prescriptions over a multiyear period and demographic characteristics associated with receipt of TABLE 4 Multivariate Logistic Regression of Patient Characteristics Associated With Receipt of Antihypertensive Prescription for Medicaid Adolescents With Primary HTN (N = 4296) OR P Value 95% CI Male (ref = female) Age at first eligibility 2.11, y (ref = y) White (ref = black) 1.61, Hispanic (ref = black) Other/unknown (ref = black) Has obesity comorbidity (ref = no comorbidity) 1.57, y of Medicaid eligibility (ref = 3 y) ref, reference. antihypertensive prescriptions. Additionally, our study provides the first look at patterns of antihypertensive prescribing for adolescents with primary HTN including the use of monotherapy versus combination therapy by physicians of different specialties and factors associated with receipt of combination antihypertensive therapy. In our study, white adolescents were significantly more likely to receive antihypertensive prescriptions compared with black subjects when controlling for obesity-related comorbidity, patient age, and gender, as well as years of Medicaid eligibility. Previous studies of US adults have documented race disparities in HTN prevalence with non- Hispanic black subjects having higher risk for HTN, CVD, and stroke compared with non-hispanic white subjects and Mexican-American subjects. 8 Our study suggests that race differences exist in physicians prescribing of antihypertensives to adolescents with primary HTN. Importantly, we also found that black adolescents were more likely to receive combination therapy compared with white subjects when controlling for other patient characteristics and specialty of prescribing physician. Taken together, these findings may reflect potential undertreatment or delay in treatment of HTN in black subjects. Increased use of combination therapy in black subjects may also reflect more aggressive BP control given that black adolescents with primary HTN have PEDIATRICS Volume 129, Number 1, January

6 TABLE 5 Multivariate Logistic Regression of Patient Factors and Prescribing Physician Specialty Associated With Receipt of Combination Antihypertensive Prescription for Medicaid Adolescents With Primary HTN (n = 977) OR P Value 95% CI Female (ref = male) Age at first eligibility y (ref = y) Black (ref = white) Hispanic (ref = white) Other/unknown (ref = white) Has obesity comorbidity (ref = no comorbidity) y of Medicaid eligibility (ref = 3 y) Adult PCP only (ref = Spec only) Pediatric PCP only (ref = Spec only) Both PCP + Spec (ref = Spec only) Both adult PCP + pediatric PCP (ref = Spec only) Unknown (ref = Spec only) ref, reference. higher risk of CVD compared with nonblack adolescents. 9 Previous studies of adults with HTN have shown black subjects to be less responsive to monotherapy and thus often requiring treatment with drugs from 2 or more antihypertensive drug classes. 10 Additional study of physician decision making, as well as clinical outcomes, is warranted to better understand the racial patterns observed in this study. Our study also found that older adolescents and those with obesity-related comorbidities were more likely to receive antihypertensive prescriptions compared with younger adolescents and those without comorbidity when controlling for patient gender and race. Older adolescents were also more likely to receive combination therapy. This is consistent with previous work 11 and with clinical experience; older adolescents are more likely to have longer duration of disease, higher severity of disease, and/or episodes of treatment failures. Moreover, guidelines recommend pharmacotherapy to treat HTN in adolescents with comorbid conditions; thus, our findings are consistent with treatment recommendations according to national guidelines. 7 Antihypertensive medications were prescribed most frequently by adult PCPs in our study. Elevated BP values indicating hypertensive range for adolescents (eg, 122/80 for a 12-year-old boy at the lowest height quartile) begin to resemble pre-htn (120/80) for adults, indicating increased risk of heart disease and stroke. 4,7,12 Thus, it is likely that adult PCPs familiar with management of HTN in adults have improved awareness and detection of abnormally elevated BP values requiring pharmacotherapy in adolescents. Moreover, adult PCPs, who often initiate and manage pharmacotherapy in treatment of HTN in adults, are likely as comfortable prescribing antihypertensive medications to adolescents as adults. In contrast, our study found that general pediatric PCPs and Specs were less frequent prescribers of antihypertensive medications for adolescents. A previous study suggests that only 7% of general pediatric PCPs initiate pharmacologic treatment of adolescents with primary HTN, 13 and it seems plausible that lack of familiarity with antihypertensive medications may play a role in this low rate. In addition, we have previously described pediatric cardiologists and nephrologists reluctance to initiate recommended antihypertensive pharmacotherapy in children with primary HTN. 14 Additional studies are needed to elucidate the underlying factors related to prescribing of antihypertensive pharmacotherapy in adolescents with primary HTN. The use of combination antihypertensive pharmacotherapy suggests increased severity of illnesswhereoptimal BP control cannot be achieved on monotherapy. In our study, more than a quarter of Medicaid adolescents with primary HTN who received antihypertensive prescriptions were prescribed combination therapy. Importantly, we found that adolescents receiving combination therapy from physicians of multiple specialties during the study period received it more often in the form of multiple drugs that raise questions of medical comanagement and whether the use of multiple antihypertensives is coordinated between prescribers of different specialties. One rationale for prescribing multiple-drug combination therapy is cost; 4 of 5 recommended monotherapy drug classes have generic options available, whereas combination pills are relatively more new without generic options. 15 However, it is unknown whether there are differences in patient outcomes related to drug safety and efficacy using antihypertensive combination therapy prescribed as combination pill versus multiple drugs in adolescents with HTN. Further study is needed to evaluate treatment decisions and patient outcomes regarding the use and choice of different forms of combination therapy (1 pill vs multiple drugs) in adolescents with primary HTN by physicians of different specialty training. LIMITATIONS Our findings should be interpreted with these limitations. First, our study population was adolescents enrolled in the Michigan Medicaid program, which has potential implications for generalizability of our results. Second, limitations of pharmacy claims analysis suggest prescription claims that were filled, which may potentially differ from utilization. Third, we examined prescription claims at the level of drug class, not individual drugs. We were 6 YOON et al

7 ARTICLE unable to determine whether maximal dose of monotherapy was achieved before adolescents were transitioned to combination therapy, if any. Fourth, formulary restrictions could potentially affect physician prescribing of newer antihypertensive medications such as ARBs. However, we had previously demonstrated that the Michigan Medicaid program offered more ARBs, BBs, and calcium channel blockers as preferred drugs when compared with a private insurance plan during a similar time period. 15 Finally, we acknowledge leftcensoring issue where we cannot evaluate antihypertensive prescritions prescribed before CONCLUSIONS Adult PCPs were leading prescribers of antihypertensive medications for adolescents with primary HTN. Race differences exist in physicians prescribing of antihypertensives to adolescents with primary HTN; white adolescents are more likely to receive antihypertensives compared with black subjects. The choice of antihypertensive medications by physicians of different specialties warrants additional study to understand the underlying rationale for those decisions and to determine treatment effectiveness. ACKNOWLEDGMENTS This study was funded by the National Heart, Lung, and Blood Institute (EYY K23 HL ). Dr Yoon had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. REFERENCES 1. McNiece KL, Poffenbarger TS, Turner JL, Franco KD, Sorof JM, Portman RJ. Prevalence of hypertension and pre-hypertension among adolescents. JPediatr. 2007;150(6): e1 2. Muntner P, He J, Cutler JA, Wildman RP, Whelton PK. Trends in blood pressure among children and adolescents. JAMA. 2004;291(17): Sorof J, Daniels S. Obesity hypertension in children: a problem of epidemic proportions. Hypertension. 2002;40(4): Rosendorff C, Black HR, Cannon CP, Gersh BJ, Gore J, Izzo JL Jr, et al. Treatment of hypertension in the prevention and management of ischemic heart disease: a scientific statement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention. Circulation. 2007;115(21): Hansen ML, Gunn PW, Kaelber DC. Underdiagnosis of hypertension in children and adolescents. JAMA. 2007;298(8): Kaelber DC, Pickett F. Simple table to identify children and adolescents needing further evaluation of blood pressure. Pediatrics. 2009;123(6). Available at: www. pediatrics.org/cgi/content/full/123/6/e National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004; 114(suppl 2): Keenan N, Rosendorf KA. Prevalence of hypertension and controlled hypertension United States, MMWR Surveill Summ. 2011;(suppl 60): Brady TM, Fivush B, Parekh RS, Flynn JT. Racial differences among children with primary hypertension. Pediatrics. 2010;126(5): Flack JM, Saunders E, Gradman A, Kraus WE, Lester FM, Pratt JHet alstudy Group for Losartan in African Americans with Hypertension. Antihypertensive efficacy and safety of losartan alone and in combination with hydrochlorothiazide in adult African Americans with mild to moderate hypertension. Clin Ther. 2001;23(8): Cox ER, Halloran DR, Homan SM, Welliver S, Mager DE. Trends in the prevalence of chronic medication use in children: Pediatrics. 2008;122(5). Available at: National Heart, Lung, and Blood Institute. What is high blood pressure? Diseases and conditions index. Available at: nih.gov/health/dci/diseases/hbp/hbp_whatis.html. Accessed August 2, Boneparth A, Flynn JT. Evaluation and treatment of hypertension in general pediatric practice. Clin Pediatr (Phila). 2009; 48(1): Yoon EY, Davis MM, Rocchini A, Kershaw D, Freed GL. Medical management of children with primary hypertension by pediatric subspecialists. Pediatr Nephrol. 2009;24(1): Yoon EY, Davis MM, Kershaw DB, Clark SJ. Formulary coverage for antihypertensive drugs used in children. Am J Pharm Benefits. 2009;1(3): PEDIATRICS Volume 129, Number 1, January

8 APPENDIX ICD-9-CM Codes for Study Inclusion and Exclusion Criteria ICD-9-CM Diagnosis Codes Inclusions Primary HTN 401x, Exclusions Malignant HTN 4010 Pregnancy 630x 679x, V22x V24x, V26x, 761x 763x, 767x, 768x, 760.0, 760.1, Portal HTN 452x, 570x Pulmonary HTN 415x 417x Glaucoma 365x Secondary HTN 402x 405x Common causes of pediatric secondary HTN Congenital anomalies 753x, 747.1, Diseases of the circulatory system 444x, 446x, 447x, Diseases of the genitourinary system 580x 594x Diseases of the musculoskeletal system and connective 710x, 720x tissue Diseases of the nervous system and sense organs 325x, 326x, 3272, 3240, 3249, 3482 Endocrine, nutritional, and metabolic diseases; 240x 246x, 252x, 253x, 255x, immunity disorders Neoplasms 189x, 191x, 193x, 194x, 223x, 225x 227x, 237 Polycythemia Chronic respiratory disease arising in the perinatal period YOON et al

9 Antihypertensive Prescribing Patterns for Adolescents With Primary Hypertension Esther Y. Yoon, Lisa Cohn, Albert Rocchini, David Kershaw, Gary Freed, Frank Ascione and Sarah Clark Pediatrics originally published online December 5, 2011; Updated Information & Services Permissions & Licensing Reprints including high resolution figures, can be found at: Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: Information about ordering reprints can be found online:

10 Antihypertensive Prescribing Patterns for Adolescents With Primary Hypertension Esther Y. Yoon, Lisa Cohn, Albert Rocchini, David Kershaw, Gary Freed, Frank Ascione and Sarah Clark Pediatrics originally published online December 5, 2011; The online version of this article, along with updated information and services, is located on the World Wide Web at: Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, Copyright 2011 by the American Academy of Pediatrics. All rights reserved. Print ISSN: